PMID- 24949855
OWN - NLM
STAT- MEDLINE
DCOM- 20151013
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 6
DP  - 2014
TI  - A systems biology approach to the analysis of subset-specific responses to 
      lipopolysaccharide in dendritic cells.
PG  - e100613
LID - 10.1371/journal.pone.0100613 [doi]
LID - e100613
AB  - Dendritic cells (DCs) are critical for regulating CD4 and CD8 T cell immunity, 
      controlling Th1, Th2, and Th17 commitment, generating inducible Tregs, and 
      mediating tolerance. It is believed that distinct DC subsets have evolved to 
      control these different immune outcomes. However, how DC subsets mount different 
      responses to inflammatory and/or tolerogenic signals in order to accomplish their 
      divergent functions remains unclear. Lipopolysaccharide (LPS) provides an 
      excellent model for investigating responses in closely related splenic DC 
      subsets, as all subsets express the LPS receptor TLR4 and respond to LPS in 
      vitro. However, previous studies of the LPS-induced DC transcriptome have been 
      performed only on mixed DC populations. Moreover, comparisons of the in vivo 
      response of two closely related DC subsets to LPS stimulation have not been 
      reported in the literature to date. We compared the transcriptomes of murine 
      splenic CD8 and CD11b DC subsets after in vivo LPS stimulation, using RNA-Seq and 
      systems biology approaches. We identified subset-specific gene signatures, which 
      included multiple functional immune mediators unique to each subset. To explain 
      the observed subset-specific differences, we used a network analysis approach. 
      While both DC subsets used a conserved set of transcription factors and major 
      signalling pathways, the subsets showed differential regulation of sets of genes 
      that 'fine-tune' the network Hubs expressed in common. We propose a model in 
      which signalling through common pathway components is 'fine-tuned' by 
      transcriptional control of subset-specific modulators, thus allowing for distinct 
      functional outcomes in closely related DC subsets. We extend this analysis to 
      comparable datasets from the literature and confirm that our model can account 
      for cell subset-specific responses to LPS stimulation in multiple subpopulations 
      in mouse and man.
FAU - Hancock, David G
AU  - Hancock DG
AD  - Centenary Institute of Cancer Medicine and Cell Biology, New South Wales, 
      Australia; The Discipline of Dermatology, University of Sydney, New South Wales, 
      Australia.
FAU - Shklovskaya, Elena
AU  - Shklovskaya E
AD  - Centenary Institute of Cancer Medicine and Cell Biology, New South Wales, 
      Australia; The Discipline of Dermatology, University of Sydney, New South Wales, 
      Australia.
FAU - Guy, Thomas V
AU  - Guy TV
AD  - Centenary Institute of Cancer Medicine and Cell Biology, New South Wales, 
      Australia; The Discipline of Dermatology, University of Sydney, New South Wales, 
      Australia.
FAU - Falsafi, Reza
AU  - Falsafi R
AD  - Centre for Microbial Diseases & Immunity Research, University of British 
      Columbia, Vancouver, British Columbia, Canada.
FAU - Fjell, Chris D
AU  - Fjell CD
AD  - Centre for Microbial Diseases & Immunity Research, University of British 
      Columbia, Vancouver, British Columbia, Canada; James Hogg Research Centre, 
      University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, 
      Canada.
FAU - Ritchie, William
AU  - Ritchie W
AD  - Centenary Institute of Cancer Medicine and Cell Biology, New South Wales, 
      Australia.
FAU - Hancock, Robert E W
AU  - Hancock RE
AD  - Centre for Microbial Diseases & Immunity Research, University of British 
      Columbia, Vancouver, British Columbia, Canada.
FAU - Fazekas de St Groth, Barbara
AU  - Fazekas de St Groth B
AD  - Centenary Institute of Cancer Medicine and Cell Biology, New South Wales, 
      Australia; The Discipline of Dermatology, University of Sydney, New South Wales, 
      Australia.
LA  - eng
GR  - MOP-74493/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140620
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CD11b Antigen)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - CD11b Antigen/biosynthesis/immunology
MH  - CD4-Positive T-Lymphocytes/drug effects/immunology
MH  - CD8-Positive T-Lymphocytes/*drug effects/immunology
MH  - Dendritic Cells/drug effects/*immunology
MH  - Gene Expression Regulation/drug effects
MH  - Immune Tolerance
MH  - Immunity/*drug effects
MH  - Immunophenotyping
MH  - Lipopolysaccharides/administration & dosage
MH  - Lymphocyte Activation/drug effects/immunology
MH  - Mice
MH  - *Systems Biology
MH  - T-Lymphocytes, Helper-Inducer/drug effects/immunology
MH  - Th1 Cells/drug effects/immunology
MH  - Toll-Like Receptor 4/biosynthesis/immunology
PMC - PMC4065045
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/06/21 06:00
MHDA- 2015/10/16 06:00
PMCR- 2014/06/20
CRDT- 2014/06/21 06:00
PHST- 2013/11/15 00:00 [received]
PHST- 2014/05/28 00:00 [accepted]
PHST- 2014/06/21 06:00 [entrez]
PHST- 2014/06/21 06:00 [pubmed]
PHST- 2015/10/16 06:00 [medline]
PHST- 2014/06/20 00:00 [pmc-release]
AID - PONE-D-13-48052 [pii]
AID - 10.1371/journal.pone.0100613 [doi]
PST - epublish
SO  - PLoS One. 2014 Jun 20;9(6):e100613. doi: 10.1371/journal.pone.0100613. 
      eCollection 2014.